Computer Vision for Kinetic Analysis of Lab- and Process-Scale Mixing Phenomena

A software platform for the computer vision-enabled analysis of mixing phenomena of relevance to process scale-up is described. By bringing new and known time-resolved mixing metrics under one platform, hitherto unavailable comparisons of pixel-derived mixing metrics are exemplified across non-chemical and chemical processes. The analytical methods described are applicable using any camera and across an appreciable range of reactor scales, from development through to process scale-up. A case study in nucleophilic aromatic substitution run on a 5 L scale in a stirred tank reactor shows how camera and offline concentration analyses can be correlated. In some cases, it can be shown that camera data hold the power to predict reaction progress.


General Considerations
The videos were recorded at a frame rate of 30 Hz and a spatial resolution of 1920 × 1080. 1 H spectra were recorded on a Bruker AVIII-400 spectrometer at 400 MHz.
Chemical shifts are reported in ppm. Coupling constants are reported in Hz. The following chemicals were employed:  Bromothymol blue ACS reagent dye content 95% (SIGMA-ALDRICH)  Sodium hydrogen carbonate, ≥ 99% (Fisher Scientific)  N,N-dimethylformamide for peptide synthesis (Rathburn).

Sodium Hydrogen carbonate
Sodium hydrogen carbonate (392 g, 4.666 mol) was added to a 3.5 L beaker with 2 L water at 20 °C to give a saturated sodium hydrogen carbonate aqueous solution with approx. 200 g suspended particulate. A Heidolph RZR 2040 overhead stirrer fitted with an anchor or paddle stirrer was employed at a height of 1.5 cm above the bottom of the beaker. Apparatus was stationed in a GODOX LST60 LED mini photography tent 60 × 60 × 60 cm lightbox. OBS studio and a Microsoft LifeCam Studio 1425 were employed as recording software and device respectively.
Recording was started and stirring commenced. The suspension was allowed to form a homogenous mixture, stirred for at least 30 seconds, then stirring was ceased and the suspension allowed to settle. A simulated probe was added by affixing a 25 × 8 cm cylindrical Teflon magnetic stir bar retriever at 0.5 cm height from the bottom of the beaker and 3 cm from the side. Experiments were repeated at 60, 100 and 210 rpm for both anchor and paddle stirrers and vessels containing a simulated probe and no probe.

Nucleophilic Aromatic Substitution
This reaction was scaled up from a published procedure. 1  Experiment was repeated at 50 rpm and an anchor stirrer. On the repeat an excess (~ 500 mL) of N,N-dimethylformamide was used.

Bromothymol Blue in Beaker
This preparation was adapted from a published procedure. 2  Experiments were repeated at 200 rpm for both anchor and paddle stirrers, in the presence of mock in-house manufactured baffles or without. Another repetition was performed without stirring for an exaggerated example of "bad" mixing.

Bromothymol Blue in STR
An aqueous alkaline bromothymol blue was prepared analogously as in the experiments conducted in the beaker scaled up to 3 L. This was added to a Radleys

Villermaux-Dushman Reaction
Quantities used were adapted from published procedures. 3 Figure S4 1 H-NMR spectra of reaction mixture after quench at 0 minutes in nondeuterated DMF.

Figure S5
1 H-NMR spectra of reaction mixture after quench at 5 minutes in non-

Kineticolor and Video Analysis
As described at the conceptual level in manuscript Scheme 1, and in our previous publication, 4 Kineticolor operates on the basis of video (mp4, mov, or avi) video input. The software breaks the video into its component frames and conducts a series of averaged and spatially-resolved computations based on pixel analysis.
All raw spreadsheet outputs for averaged and spatially-resolved mixing metrics, for all reactions discussed in the manuscript, are provided in an accompanying zipped folder of Excel files.
In all cases (except in cases specified in the folder), files contain the following tabs: